CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

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processes. Although the aspects of their toxicity and disposal have not been fully explored yet, the use of ionic liquids can definitely make a contribution in this area, particularly with regard to solvent and catalyst usage. IIII. .33. .22 IInnddi iuum meeddi iaat teedd aal llyyl laat tioonn inn i [bbmi[ im] ][Brr] ] Indium mediated allylation of carbonyl compounds to give the corresponding homoallylic alcohol has been extensively studied in the past two decades, 65a,73 especially with the discovery that the reaction can be carried out in aqueous media. 64b,65b,74 As opposed to other metals, In is less air- and moisture-sensitive, significantly less toxic, and able to tolerate numerous functionalities offering advantages for the allylation reactions. 64,75 In this investigation, we used In as the metal mediator and [bmim][Br] as the solvent to develop an efficient method for allylation of aldehydes. In general, only the hydrophobic RTILs are used for the Barbier type reactions. The simplest RTIL, [bmim][Br] has so far been used for bromination of arylamines and α,β-unsaturated carboxylic acids, synthesis of cyclic urethane and pyrimidinediones, 76a,b dealkylation of aryl alkyl ethers, 76c and most interestingly for Heck reaction. 69e However, due to its excellent hydrophilicity, it was expected to mimic aqueous medium and appeared best suited for the Barbier type reactions. This study also provided new mechanistic insights in the allyl-In chemistry in [bmim][Br], eventually leading to a protocol with catalytic quantity of In. 39
RCHO 59a-j i R OH 60a-j (i) Allyl bromide, In, solvent. Scheme II.3.2 Initially, the In-mediated allylation of benzaldehyde (59a) was carried out in H 2 O, THF and three different RTILs, including [bmim][Br], and the results (Scheme II.3.2, Table II.3.1) established the efficacy of [bmim][Br] as the best solvent. Table II.3.1. Reaction profile of the In-mediated allylation of different aldehydes in various solvents a entry substrate R allyl bromide (equiv.) metal (equiv.) solvent time (h) product 1 59a C 6 H 5 3 5 H 2 O 18 60a 59 2 59a C 6 H 5 3 5 THF 18 60a 65 3 59a C 6 H 5 1.5 1.2 [bmim][Br] 4 60a 89 4 59a C 6 H 5 1.5 1.2 [bmim][BF 4 ] 20 60a 64 5 59a C 6 H 5 1.5 1.2 [bmim][PF 6 ] 20 60a 62 6 59b 4-BrC 6 H 4 1.5 1.2 [bmim][Br] 4 60b 88 7 59h (CH 3 ) 2 CH 1.5 1.2 [bmim][Br] 5 60h 68 8 59i CH 3 (CH 2 ) 5 1.5 1.2 [bmim][Br] 5 60i 81 a The reactions were carried out at 2 mmol scale. b Isolated yields of the products. yield (%) b 40
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ASYMMETRIC STRATEGIES FOR THE SYNTH
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ACKNOWLEDGEMENTS First of all, I wa
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CONTENTS SYNOPSIS LIST OF FIGURES L
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SYNOPSIS
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models (e. g. Cram’s model, Felki
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4 1d 4-(CH 3 ) 2 CH-C 6 H 4 1 : 1.5
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14. 1n C 6 H 5 CO C 6 H 5 2n 8 77 1
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imetallic systems. In all the cases
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For the benzylation reaction, the c
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O O 3 CHO i O O + OH 13a O O OH O O
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10 3.5 Ga (2.5) THF KI+LiCl 10 55 5
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multidrug-resistant (MDR) cancer ce
Page 29 and 30: directly afforded the furanose, whi
Page 31 and 32: References 1. Stephenson, G. R. Adv
Page 33 and 34: LIST OF FIGURES
Page 35 and 36: II.3.13 III.1.1 III.1.2 III.1.3 III
Page 37 and 38: IV.5.2 IV.5.3 IV.5.4 IV.5.5 1 H NMR
Page 39 and 40: Table Title Page No. II.3.1 II.3.2
Page 41 and 42: II. .11 PPREAMBLE Demand for specia
Page 43 and 44: II. .22 IINTRODUCTIION TO CHIIRALII
Page 45 and 46: The most dramatic example in this a
Page 47 and 48: H H 2 N OH COOH i PhH 2 CO O H N H
Page 49 and 50: Methods of Asymmetric Synthesis: 15
Page 51 and 52: O O O O i, ii iii iv HO HO N N OH O
Page 53 and 54: Models for Asymmetric Synthesis. 21
Page 55 and 56: If a strongly electronegative group
Page 57 and 58: enantiomeric products are formed at
Page 59 and 60: vi) The balance between chiral auxi
Page 61 and 62: IIII. .11 IINTRODUCTIION TO CHIIRAL
Page 63 and 64: Scheme II.1.2 However, availability
Page 65 and 66: Prof. R. Noyori received the Nobel
Page 67 and 68: Apart from the cinchona alkaloids,
Page 69 and 70: ligand, it assumes a tetrahedral co
Page 71 and 72: Marshall. 53 More recently, Barbero
Page 73 and 74: Various protocols have been develop
Page 75 and 76: In the absence of a sterically-bulk
Page 77 and 78: IIII. .33. . PPRESSENT WORK It is w
Page 79: [pyridinium][Sn 2 Cl 5 ] etc. can b
Page 83 and 84: Fig. II.3.2. 1 H NMR spectrum of 60
Page 85 and 86: in [bmim][BF 4 ] using sub-stoichio
Page 87 and 88: The reaction in THF was also follow
Page 89 and 90: The integration of the signal at δ
Page 91 and 92: The standard reduction potential of
Page 93 and 94: It has also been reported, 83a,b th
Page 95 and 96: IIII. .33. .33 Gaal lliuum meeddi i
Page 97 and 98: 5 3.0 5.0 THF LiCl+KI c 14 d 71 6 1
Page 99 and 100: 3 59d 4-(CH 3 ) 2 CH-C 6 H 4 H 60d
Page 101 and 102: Fig. II.3.8. 13 C NMR spectrum of 6
Page 103 and 104: Fig. II.3.10. 13 C NMR spectrum of
Page 105 and 106: fragmentation peak at m/z 138 (19%)
Page 107 and 108: Fig. II.3.13. 13 C NMR spectrum of
Page 109 and 110: active catalyst, as suggested for t
Page 111 and 112: 1-(4-Bromophenyl)-but-3-en-1-ol 59b
Page 113 and 114: 1H), 7.90-7.93 (m, 1H); 13 C NMR:
Page 115 and 116: 662, 980, 1079, 1332, 1374 cm -1 .
Page 117 and 118: IIIIII. .11 DIIASSTEREOSSELECTIIVE
Page 119 and 120: cyclohexylideneglyceraldehyde (1) 3
Page 121 and 122: mixture of Zn dust, allyl or γ-sub
Page 123 and 124: Fig. III.1.2. 13 C NMR spectrum of
Page 125 and 126: Reaction with crotyl bromide: In ca
Page 127 and 128: Fig. III.1.5. 1 H NMR spectrum of 6
Page 129 and 130: The formation of the 2,3-anti addit
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To establish the C-4 configuration
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Allylation with (E) and (Z)-1-bromo
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(i) Zn, aqueous satd. NH 4 Cl, THF,
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Fig. III.1.12. 1 H NMR spectrum of
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Allylation with 1-Bromo-4-(tert)-bu
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fast and gave a significantly bette
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espectively) due to the cyclohexyli
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Fig. III.1.19. 13 C NMR spectrum of
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was treated with excess amount of b
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Fig. III.1.20. 1 H NMR spectrum of
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Fig. III.1.22. 13 C NMR spectrum of
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stereochemistry of allylation of β
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of the products were modest (48-62%
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6 1.2 In (2.0) H 2 O LiCl+ KI 14 72
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are consistent with our previous re
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III.3 EXPERIMENTAL SECTION: General
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(2R,3R)-1,2-Cyclohexylidenedioxy-5-
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for an additional 2 h, gradually br
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(m, 2H), 5.82-5.98 (m, 1H), 7.25-7.
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31.6, 32.2, 63.4, 128.8, 133.0. Ana
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23 (2R,3S,4R)-1,2-Cyclohexylidenedi
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(2R,3S,4S)-1,2-Cyclohexylidenedioxy
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(m, 1H), 3.50-4.02 (m, 5H), 4.10-4.
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and dried. Removal of solvent in va
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ine, and dried. Solvent removal und
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IIV. .11 SSYNTHESSIISS OFF ENANTIIO
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Scheme IV.1.1 The same group also d
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IV.1.3: Present work Although sever
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O O C 6 H 13 i O C 6 H 13 ii OH C 6
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Fig. IV.1.4. 1 H NMR spectrum of 10
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the unit-C contribute positively to
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tartrate, Ti(O-i-Pr) 4 , CH 2 Cl 2
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Based on this hypothesis, the alcoh
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OR 3 O R 1 R 2 NaBH 4 H H R 1 R 1 +
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(OH). Oxidative cleavage of its α-
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IIV. .33: : SSYNTHESSIISS OFF 33' '
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For the actual synthesis, (Scheme I
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IV.4: SSYNTHESSIISS OFF 22( (SS) )-
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(i) PhCHO, triethyl orthoformate, M
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O N 3 II Ph HO OH b1 N 3 Ph O O Ben
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Thus, easily accessible 1 has been
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167 and subsequent reduction gave 1
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from the appearance of 13 C NMR pea
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IV.6 EXPERIMENTAL SECTION (2R,3S,4R
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As described earlier, compound 108
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19.5, 23.8, 23.9, 25.1, 26.9, 34.6,
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74.2, 74.4, 110.1, 116.7, 127.6, 12
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mmol) in MeOH (10 mL), work up, fol
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7.51 (m, 3H), 7.92-8.08 (m, 2H); 13
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subsequent isolation afforded rotam
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4.18 (t, J = 3.4 Hz, 1H), 4.75-4.84
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-4.21 (c 1.2, CHCl 3 ); IR: 3466, 1
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(3R)- 3,4-O-Cyclohexylidene-2-oxo-1
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Water and EtOAc was added to the mi
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24 179. Yield: 1.49 g (77.5%); colo
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24 furnished pure 183. Yield: 0.37
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1. Wender, P. A. Chem. Rev. 1996, 9
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17. Hanessian, S.; Maji, D. K.; Gov
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32. For some selective references s
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43. (a) Cleare, M. J.; Hydes, P. C.
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54. Barbero, A.; Pulido, F. J.; Rin
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2008, 1681. (d) Fargeas, V.; Zammat
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72. Karodia, N.; Guise, S.; Newland
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Kaminski, J.; Millhauser, G.; Ortiz
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Böhm, V. P. W.; Reisinger, C. J. O
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119. Wender, P. A.; Holt, D. A.; Si
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140. (a) Chemler, S. R.; Roush, W.
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Lett. 1996, 107, 53. (c) Smith, C.
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158. Mitsuya, H.; Weinhold, K. J.;
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L.; Zugay, J. A. J. Med. Chem. 1993
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1. Goswami, D.; Chattopadhyay, A.;
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